Bipolar Disorder (BPD) is one of the most debilitating and difficult to treat mental illnesses and it affects an estimated 4.4% of the population in the United States. Treatment of BPD involves the combined used of mood stabilizing drugs and psychotherapy. Among the mood stabilizing drugs used to treat BPD, Lithium Carbonate is an established treatment of first choice for different stages of the disease. Lithium was the first medication successfully used to treat mental illnesses. Its remarkable mood regulating properties were accidentally discovered 60 years ago and remain poorly understood to this date. Lithium has dangerous side effects that include endocrine as well as neurological ailments. These could be difficult to recognize at first and sometimes lethal in the acute setting (about 15% of subjects). Consequently, lithium treatment requires constant monitoring of serum lithium concentration (SLC) to ensure that SLC remains in the narrow therapeutic range of 0.6 to 1.2mM. However, use of this therapeutic range only leads to a successful outcome in less than 50% of the subjects. Brain Lithium Concentration (BLC) is accepted to be a better predictor of therapeutic response than SLC. The lithium ion is NMR active and, therefore, measurable with magnetic resonance spectroscopy (MRS) when whole-brain MRS is used. Use of whole-brain MRS acquisitions, however, leads to lower accuracy and reproducibility for BLC, it underestimates the peak concentration of the drug and cannot provide critically important information about the spatial accumulation of the drug. This proposal is aimed at developing a methodology for in vivo three dimensional lithium imaging using magnetic resonance imaging (MRI) and establishing if the increase in BLC that follows lithium administration can be indirectly observed by monitoring the normalization of brain sodium concentration (BSC) that it induces. Because the normalization of BSC is easily measurable in a quantitative fashion with MRI, this methodology could provide a tool for better management of the disease and understanding its mechanisms of action in the brain. The effectiveness of the proposed methodology is to be tested on BPD subjects recruited through the clinical infrastructure of the Western Psychiatric Institutes and Clinic at the University of Pittsburgh. PUBLIC HEALTH RELEVANCE: This proposal aims to develop a methodology for improving the management of Bipolar Disease Subjects using MRI technology. The goal is to develop a technique that allows the measurement of lithium accumulation in the brain with MRI as this is accepted to be a better predictor of outcome than the serum lithium content (which is a critical clinical variable currently used to manage the disease).